fbom the potassium salt of i-diethylamino-



United States Patent BENZ-QUINOLINE COMPOUNDS AND PROCESS FOR THE MANUFACTURE THEREOF Franz Bergel, London, Aaron Cohen, Frank Ratcliffe Atherton, and Basil Heath-Brown, Welwyn Garden City, and Edward Graham Hughes, Runcorn, England, assignors to lloiimaun-La Roche Inc., Nutley, N. J., a corporation of New Jersey No Drawing. Application March 17, 1952, Serial No. 277,092

Claims priority, application Great Britain March 22, 1951 11 Claims. (Cl. 260-486) The present invention is concerned with l-methyl- 1,2,3,4-tetrahydro 5,6 benz quinoline 3 carboxylic acid, 1 methyl l,2,3,4 tetrahydro-S,6-benz-quinoline- 3-carboxylic acid methylamide, novel intermediates used in the manufacture thereof, and with aprocess for the manufacture of these substances and said intermediates.

According to the invention there is provided a process which comprises treating a l-dialkylaminomethyl (including l-piperidinomethyland 1-1norpholinomethyl-) -2-hydroxy-naphthalene with a methane derivative of the kind CHz(X)Y, wherein X is a carbalkoxy, carbobenzyloxy or cyano and Y is a carbalkoxy or carbobenzyloxy, in the presence of an alkali-metal, converting the 3-substituted 3,4-dihydro-S,6-benz-coumarin so obtained by hydrogenolysis, when the substituent is carbobenzyloxy, or by alkaline hydrolysis into 3-carboXy-3,4 L

dihydro-5,6-benz-coumarin or [2-hydroxy-naphthyl-( 1) methyl malonic acid respectively, treating either of the latter products with a primary or secondary amine of the kind NH(R)(R"), wherein R may be hydrogen (when R" is methyl) or methyl or ethyl and R" is methyl, ethyl or benzyl, or R and R" together with the nitrogen atom represents piperidino or morpholino, and formaldehyde and heating the resulting 3-[2-hydroxy-naphthyl-(1)1- 2-carboxy-propyl amine derivative or an alkali-metal salt thereof with methylamine under pressure and, in the case where the free acid is used, hydrolysing the product.

The 3-carboxy-3,4-dihydro-5,6-benz-coumarin and the [2-hydroxy-naphthyl-( 1) ]-methyl malonic acid are interconvertible. The former can be changed into the latter by treatment with alkali while the reverse change takes place on treatment with acid. Accordingly the process described hereinbefore may be varied in that it may include such a conversion step. p

. The present invention also includes the formation of the required 1-methyl-1;2,3,4-tetrahydro-5,6-benz-quinoline-3-carboxylic acid [from [Z-hydroxy-naphthyl-(Dlmethyl malonitrile which comprises treating the latter with alkali to give [2-hydroxy-naphthyl-(1)l-methyl malonic acid which, after lactonisation if desired, is treated as indicated hereinbefore.

The 1 dialkylaminomethyl 2 hydroxy-naphthalenes more vigorous conditions, that is to say,

2,693,470 Patented Nov. 2, 1954 2 used as initial materials in the principal embodiment of the present invention may be prepared by reacting 2- hydroxy-naphthalene with the appropriate amine and formaldehyde. The [2 hydroxy-naphthyl-( 1)] methyl malonitrile used as initial material in the further embodiment of the present invention may be prepared by heating an alcoholic solution of l-dimethylaminomethyla prereduced catalyst consisting of Adams palladium oxide and 10% palladium charcoal in substantially equal amountsin a solvent such as dry ethyl acetate. The latter is effected by treatment with alkali (about two or three equivalents have been found satisfactory) under mild conditions, that is to say, without heating, followed by addition of an equivalent quantity of acid in the cold. The hydrolysis not only removes the benzyl group but opens the lactone ring to give [2-hydroxy-naphthyl-(1)lmethyl malonic acid. This substance can be used for the further steps or may be lactonized by treatment with hydrobromic acid.

The removal of the alkyl group from the 3 carbalkoxy- 3,4dihydro-5,6-benz-eoumarin is brought about by hydrolysisin a similar manner to that used for the hydrolysis of the benzyl ester and gives the same product. This product is also obtained. from 3-cyano-3,4-dihydro- 5,6-benz-coumarin and from [2-hydroxy-naphthyl-(1)]- methyl malonitrile by treatment with excess alkali under for example, by heating these substances under reflux with several moles of the alkali.

= If it is desired to open the lactone ring of the 3-carboxy- 3,4-dihydro-5,6-benz-coumarin it may be treated with cold alkali followed by treatment with an equivalent quantity of acid in the cold.

The 1-[substituted-aminomethyl]-2-[2-hydroxy-naphthyl-(l)]-propionic acids are prepared from 3-carboxy- 3,4-dihydro-5,6-benz-coumarin or from [2-hydroxy-naphthyl-(1)]-methyl malonic acid by treatment with appropriately substituted secondary amines and formaldehyde. The reaction proceeds in an aqueous medium in the cold.

The conversion of these propionic acid derivatives to l-methyl-1,2,3,4-tetrahydro-5,6-benz-quinoline-3-carboxylic acid can be brought about in either of two ways. Thus, their alkali-metal salts may be heated under pressure with methylamine or the free acids may be heated under pressure with methylamine and the resulting methylamide hydrolysed. The former method is preferred.

f {The various steps of the process may be setout as o ows:

Alkyl OH C O O Alkyl Heat alkali-metal salt 4- CHsNHz under pressure =Heat GHsNHa pressure O OOH C ONHOH hydrolysis wherein X, Y, R, R" and N(R')R have the values previously indicated.

The 1-methyl-l,2,3,4 tetrahydro 5,6 benz-quinoline-3- carboxylic acid is useful in that it has some oxytocic activity, a long-lasting narcotic activity and an analgesic action when administered in sub-narcotic doses.

The following example will serve to illustrate the invention EXAMPLE Al. The preparation of 3,4-dihydr-5,6-benz-c0umarin-3- carboxylic acid esters (it) THE ETHYL ESTER A solution of diethyl malonate (8.0 g.) in dry xylene ml.) was added to a stirred suspension of sodium powder (1.15 g.) in pure dry xylene (17.5 ml.) and warmed at 80 C. until all the sodium metal had reacted to form sodio-malonic diethyl ester. A solution of a-dimethylaminomethyl-fi-naphthol (10.5 g.) in xylene (175 ml.) was then added With stirring, the tempera:

rated or treated with light petroleum (B. P. 60-80" C.) when 3,4*dihydro-5,6-benz-coumarin-3-carboxy1ic acid ethyl ester was obtained as a white powder. This was collected, washed with water and dried. Yield: 78%. Alfger11 6recr'stallization from alcohol it melted at 1 (D) THE BENZYL ESTER (i) A solution of dibenzyl malonate (28.4 g.:0.1 mol) in toluene ml.) was added to powdered sodium (2.3 g.=0.1 mol) in toluene (100 ml.). The mixture was warmed in an oil bath (ea. 90 C.) and a clear solution was formed.

1 dimethylaminomethyl 2 hydroxy naphthalene (20.1 g.=0.1 mol) in toluene (150 ml.) was added and the mixture stirred and heated in an oil bath (ca. C.) for four and a half hours under nitrogen. The reaction mixture was allowed to stand for 16 hours and then acidified with dilute hydrochloric acid (150 ml.

' 2' N) whereby the solid dissolved and a pinkish-white solid crystallised out. This solid was filtered off and washed successively with water, benzene and petroleum ether (B. P. 40-60 C.), air dried and then dried over phosphorus pentoxide. It melted at -146 C. [Yield 17.15 g.]

The solvent phase was washed twice with sodium bicarbonate (100 ml. each) and twice with water (100 ml. each) and dried over sodium sulphate. It was then evaporated under reduced pressure to small bulk (100 ml.) and petroleum ether (B. P. 40-60 C.) was added giving an oil which solidified. The solid was filtered and triturated and washed with petroleum ether (B. P. 40-60 C.). It melted at 126-129 C. [yield=7.05 g.] which .was undepressed in a mixed melting point with the first crop. On recrystallisation from benzene (20 ml.), filtering and washing with methanol and petroleum ether (B. P. 4060 C.) crystals melting at 144-145" C. [yie1d=3.7 g.] were obtained. The combined crops (20.85 g.) were recrystallised from benzene (150 ml.) and gave crystals of pure 3- carbobenzyloxy-3,4-dihydro-5,6-benz-coumarin [yield= 17.1 g.:51% overall] which melted at 146-147" C.

(ii) The process of (i) above was repeated on twice the scale (i. e. 0.2 mol starting'materials and double quantities of solvents, etc.) except that the reactants were heated for 5 hours at 120 C. and the combined crops'were recrystallised from toluene (400 ml.). The goduct [yieldj41 g.=62% overall] melted at 146-147 A2. T he preparation of 3-cyano-3,4-dihydro-5,6=

I benz-coumarin A solution of ethyl cyanoacetate (5.65 g.) in xylene (35 ml.) was added to a stirred suspension of sodium powder (1.15 g.) in pure dry xylene (17.5 ml.) and warmed at 70-80" C. until all the sodium metal had reacted with the ethyl cyanoacetate. A solution of a-dimethylaminomethyl-B-naphthol (10.05 g.) in xylene (100 ml.) was then added, the temperature being raised to 100- 110 C., and the heating continued for 4 hours, during which period at least 87% of the dimethylamine eliminated during the course of the reaction could be trapped in a'r'eceiver containing standardacid.

The cooled reaction mixture was made acid and shaken and the solid 3-cyano-3,4-dihydro-S,6-benz-coumarin filtered off, washed with water and ether and then dried. Yield 85% as a white powder. It was purified by rapid recrystallisation from ethyl acetate and light petroleum (B. P. 60-80 C.) or from glacial acetic acid; M. P. 191 C.

A3. .The preparation of [2-hydroxy-naphthyl-(1)]- methyl-malonitrile dried. The product melted at 214-216 C. The yield amounted to 72% (239 g.).

, B1. The preparation of [Z-hydroxy-naphthyl-(J)]- methyl-malonic acid (11) BY HYDROLYSIS OF ETHYL 3,4-DIHYDRO-5,6-BENZ- COUMARIN-B-CARBOXYLATE A mixture of this ester (13.5 g.=0.5 mol) and dilute sodium hydroxide solution (125 ml. ca. 2 N) was refiuxed for three hours. At the end of this period the reaction mixture was ice-cooled and treated with a quantity of dilute hydrochloric acid equivalent-to the sodium hydroxide used for the hydrolysis. crystallisation soon commenced and the mixture was then refrigerated for several'hours. The solid was then filtered, washed with water and dried in vacuo over phosphorus pentoxide. The yield of 2-hydroxynaphthyl-(1)]-methyl-malonic acid monohydrate amounted to 79% (11 g.). The materialmeltedaat 125-126" C. with loss of carbon dioxide.

"(0) BY HYDROLYSIS OF 3-CYANO-3,4-DIHYDRO-5,6-

BENZ-COUMARIN A mixture of this compound (4.46 g.'=0.02 mol) and aqueous sodium hydroxide solution (30 ml. of was refluxed for a 'period of eight and a half hours. The hydrolysate was processed as described above and yielded similar material. The yield amounted to 77.5% (4.3 g.). 'BYHYDROLYSIS OF 3-CA'RBOXY-3A-DIHYDRO-5,6-

1 BENZ-COUMARIN This acid (2.42 g.=0.0l mol, see preparation below) Wi 91i d l t po s m. y ox d o fit 0 ml. of. 1.084 N=0.02l68 mol) and the mixture was diluted to a volume of 50 ml. After standing at room temperature for thirty minutes, 2 ml. of the reaction mixture were pippetted oif and titrated against standard hydrochloric acid. The results indicated that the reaction was virtually complete. A second titration after a further thirty minutes gave the same result.

The residual solution was ice-cooled and neutralized by the addition of an equivalent quantity of dilute hydrochloric acid (10 ml. of 2 N). When crystallisation had proceeded for one hour the crystalline product was filtered off, washed with water and dried in vacuo over phosphorus pentoxide. The yield of [2-hydroxy naphthyl (1)] methyl malonic acid monohydratc amounted to 65% (1.65 g.).

((2) BY HYDROLYSIS OF [2-HYDROXY-NAPHTHYL-(1) METHYL-MALONITRILE I (6) BY HYDROLYSIS OF BENZYL 3,4-DIHYDRO-5,6- BENZ-COUMARIN-3-CARBOXYLATE A mixture of the above ester (16.6 g.'=0.05 mol), di-

lute sodium hydroxide solution m1. ca. 2 N) and ethanol (100 ml.) was shaken at 15 C. for 16 hours. The solution was then evaporated to dryness under reduced pressure (water pump), the residue dissolved in water (ca. 100 ml.) and the solution cooled to 0 C. and treated with a quantity'of dilute hydrochloric acid equivalent to the sodium hydroxide used for the hydrolysis. Further processing as (a) above yield similar material. Yield=70.5% (9.75 g.).

B2. 3-carboxy-3,4-dihydro-5,6-benz-coumarin (11) BY THE HYDROGENOLYSIS OF BENZYL 3,4-DI- HYDRO-5,6-BENZ-COUMARIN 3-CARBOXYLATE To a pre-reduced catalyst of Adams palladium oxide (02 g.).and 10% palladium charcoal (0.2 g.) in dry ethyl acetate (25 ml.) was added a solution of the above benzyl ester (4.98 g.=0.015 mol) in ethyl acetate ml.). The mixture was then shaken in a hydrogen atmosphere until absorption ceased (365 ml. in two hours). The catalyst was filtered and the filtrate was evaporated in vacuo to a volume of ca. 75 ml. and treated with petrol. The precipitated solid was filtered and washed with petrol. After, air drying, the yield of 3,4- dihydro-5,6-benz-coumarin-3-carboxylic acid amounted to 76% (2.75 g.). It melted at 124-125 C. and had an equivalent weight of 239 (theory 242).

(b) BY CYCLISATION OF [2-HYDROXY-NAPHTHYL-(1) METHYL MALONIC ACID The above acid (27.8 g.=0.1 mol) was dissolved in glacial acetic acid (50 ml.) with slight warming (not morethan 45 .C.), the solutioncooled and treated with a saturated solution of hydrogen bromide in acetic acid (5 ml.). Crystallisation commenced almost at once. After irty minutes, a mixture of benzene (100 ml.) and petrol (100 ml.) was added and the solid was filtered and washed. with benzene/petrol and finally petrol. The crude material, M. P. 142-143" C., was dried over phosphorus pentoxide and potassium hydroxide. This material (24.05 g.) was dissolved in hot acetone (100 ml.), the solution charcoaled and filtered and diluted with 40/ 60 petrol (100 ml.) until crystallisation commenced. After some time, a further amount of petrol (100 ml.) was added and the solid was filtered ofi' and washed with petrol. The mother liquors were evaporated and the crude solid recrystallised in the same way The combined crops (19.25 g. 2.5 g.) of 3,4-dihydro-5,6-benzcoumarin-3-carboxylic acid amounted to 90% (21.75 g.).

alent weightof240 (theory 242). i

C1. 1 [substituted-aminomethyl] -2* [2'-hydroxynaphthyl-(I l-propionic acids I -dimethyIaminOmeIhyI-Z-[2'-hydroxy-naphthyl- 1') l-propionic acid (0.) FROM [2-HYDROXY-NAPHTHYL-(1) ]-METHYL- BIALONIC ACID [2-hydroxy-naphthyl-(1) l-methyl-malonic acid (69.5 g.=0.25 mol) in water (250 ml.) was treated with an aqueous solution of dimethylarnine (50 ml. of 22.5% w./v.=0.25 mol). The mixture was cooled to C. and formalin (18.75 ml. 40% w./v.) was added and the reaction mixture was allowed to stand at room temperature for five days.

The separated solid was filtered, washed with methanol and acetone and air dried. The mother liquors concentrated to low bulk gave a further amount of the same material. The yield of 1-dimethylaminomethyl-2-[2-hydroxy-naphthyl-(l)l-propiouic acid amounted to 90% (61.4 g.). It melted at 190l92 C.

(1)) FROM 3-CARBOXY-3A-DIHYDR05,6-BENZ- COUMARIN The above acid (2.21 g.) in water ml.) was treated with an aqueous solution of dimethylamine (1.83 ml. 22.5% W./v. and the mixture was cooled, treated with formalin (0.685 ml. of 40% w./v.) and kept for 5 days in the refrigerator. The solution was evaporated in vacuo and the residue was treated with acetone (50 ml.). The solid was filtered and washed with acetone. Thls material was not completely pure and melted at 175- 177 C. The properties and analysis were those of the required 1 dimethylaminomethyl 2-[2'-hydroxy-naphthyl-(l')]-propionic acid. Yield=57% (1.55 g.).

C2. 1 -diethylaminomethyl-2- [2'-hydr0xy-naphthyl- (1 l-propi0nic acid [2-hydroxy-naphthyl-( 1 l-methyl-malonic acid 11.1 g.=0.04 mol) in water (40 ml.) was treated with diethylamine (2.92 g.=0.04 mol). The mixture was cooled to 0 C. and formalin (3 ml. 40% w./v.) was added and the reaction mixture was allowed to stand at room temperature for 9 days. The mixture was then evaporated under reduced pressure and the residue taken up on acetone and allowed to crystallise. This crystalline product was filtered and washed with acetone. In order to obtain pure material it was necessary to recrystallise from methyl ethyl ketone. This treatment gave pure l-dieth'ylaminomethyl 2 [2' hydroxynaphthyH 1) ]-propionic acid. The yield amounted to 32.5% (3.9 g.) and the compound had M. P. 147-148 C.

C3. 1-m0rph0lin0methyl-2- [2-hydr0xy-naphthyl- (1 l-propionic acid This was obtained by replacing the diethylamine in the procedure of the foregoing section 2 by an equivalent amount of morpholine (3.48 g.=0.04 mol). Further processing was carried out in a similar manner but in this instance a pure product was obtained without further recrystallisation. The yield of l-morpholinomethyl-2[2" hydroxy naphthyl-(1')]propionic acid monohydrate amounted to 64% (8.6 g.). It melted at 105-107 C.

C4. I-piperidinomethyl-Z-[2'-hydr0xynaphthyl- (1') l-propionic acid This was obtained by replacing the morpholine of section 3 by an equivalent amount of piperidine (3.40 g. =0.04 mol). Processing was carried out in an exactly similar manner. The yield of lpiperidinomethyI-2-[2- hydroxy naphthyl (l')]-propionic acid monohydrate amounted to 45.5% (6.05 g.). It melted at 122-125 C.

C5. 1-methylamin0methyl-2-[2-hydroxy-naphthyl- (1')]-pr0pionic acid The .diethylarnine of section 2 was replaced by an equivalent quantity of aqueous methylamine solution (3.05 g. 40.7% w./v.=0.04 mol) and the mixture was kept at C. for 14 days. Evaporation of the reaction mixture left a gummy residue which solidified on trituration with ethyl acetate. This crude product was dissolved in methanol and the solution evaporated to low bulk, treated with acetone and refrigerated for 24 hours. The solid was filtered and washed with acetone. The yield of l-methylaminomethyl-Z-[2'-hydroxy-naphthyl- (1')]-propionic acid amounted to 11% (1.15 g). It

melted at 185-187 C.

C6. 1-[N-benzyl-N-methybaminomethyl]-2-[2'- hydroxy-naphthyl-(l ]pr0pi0nic acid (11') FROM [2-HYDROXY-NAPH'1HYL- 1) 1 Murmur MALONIC ACID This was obtained by replacing the morpholine in section 3 by an equivalent quantity of methylbenzylamine. Processing was carried out in the same manner. The yield of l benzyl-methylaminomethyl-2-[2'-hydroXy nahpthyl-(l') ]-propionic acid hemihydrate amounted to 28% (4.0 g.). It melted at 17l C.

(21) FROM 3-CARBOXY'3A-DIHYDRO-5,G-BENZ- C0 UMARIN D. 1-methyl-1,2,3,4-tctrahydr0 5,6 benz quinoline-3- carboxylic acid ((1) FROM: l"DIBIIi]THYLAMIINODIETHYLMZ-[2'HYDRUXY NAPHTHYL-'(l') ]PROPIONIC ACID 1 dimethylaminomethyl 2 [2' hydroxy-naphthyl- (1)]-propionic acid (2.73 g.=0.0l mol) and excess aqueous methyiamine solution (15 ml. of 40% w./v.) were heated to 200 C. in a sealed tube for eighteen hours. At the end of this period the tube was cooled and the contents diluted with an equal volume of water. The crystalline solid which separated was filtered, washed with water and dried in vacuo over phosphorus pentoxide. Its properties showed it to be the methylamide of the required acid. The yield amounted to 63% (1.60 g.); the compound melted at 170-174 C.

The filtrate was concentrated to dryness in vacuo and the residue dissolved in water (20 ml.) and treated with concentrated hydrochloric acid 5 ml.). On standing,

crystalline material deposited. T is was filtered, washed with dilute hydrochloric acid and acetone and air dried. It proved to be the hydrochloride of the required aminoacid. The yield amounted to 32.5% (0.9 g.) and the compound melted at 207209 C.

The free amino-acid may be obtained by shaking the hydrochloride with sodium acetate solution. It melted at 154-156 C.

(b) FROM THE POTASSIUM SALT OF l-DIMETHYL- AMINOMEIHYL 2 [2 HYDROXY NAPHTHYL -(1)] PROPIONIC ACID The methylamide formed with the above reactions was converted to the amino-acid hydrochloride in the followmg manner.

The amide (500 mg.) was refluxed with a mixture of 2 N sodium hydroxide (15 ml.) and ethyl alcohol (2 ml.) for twenty-four hours during which period methyiamine was evolved.

After cooling, the mixture was diluted with water (10 ml.) and filtered free of traces of insoluble material. The filtrate was evaporated in vacuo to remove alcohol, diluted to ca. 20 ml. and acidified with concentrated bydrochloric acid (3.5 ml.). The solid which separated was filtered off and washed with dilute hydrochloric acid (2 N) and acetone. After air drying the yield amounted 9 to 91.5% (500 mg). It melted at 207209 C. undepressed with a genuine sample of the hydrochloride.

(d) FROM THE POTASSIUM SALT OF l-DIETHYLAMINO- METHYL 2 [2'- HYDROXY NAPHTHYL-(l' J-PROPI- ONIC ACID 1 morpholinomethyl-2-[2'-hydroxy-naphthyl (1')]- propionic acid monohydrate (1.67 g.=0.005 mol) was treated exactly as described in (d) and yielded the hydrochloride of the required amino acid (1.11 g.=80.5%

(f) FROM THE POTASSIUM SALT OF LPlPERlDINO- METHYL 2 -[2'- HYDROXY NAPHTHYL -(1) ]-PROPI- ONIC ACID 1 piperidinomethyl-Z-[2'-hydroxy naphthyl (1')]- propionic acid monohydrate (1.65 g.=0.005 mol) was treated exactly as described in (d) and yielded the hydrochloride of the required amino acid (1.11 g.=80.5%).

(g) FROM THE POTASSIUM SALT OF l-METHYLAMINO- METHYL 2 -[2'- HYDBOXY NAPHTHYL (1') ]-P.ROPI- ONIC ACID 1 methylaminomethyl-2- [2'-hydroxy-naphthyl-( 1 propionic acid (0.52 g.=0.002 mol) was dissolved in a slight excess of ca. N potassium hydroxide solution (2.05 ml. of 2.084 N) mixed with aqueous methylamine (6 ml. of 40% w./v.) and heated in a sealed tube at 160170 C. for 15 hours. Processing as described previously yielded the hydrochloride of the required amino acid (0.43 g.= 77.5%

We claim:

1. A compound of the group conslsting of 1- methyl- 1,2,3,4 tetrahydro-S,6-benz-quinoline-3-carboxylic acid, the methylamide thereof and salts thereof.

2. A salt of l-methyl-l,2,3,4-tetrahydro-5,6-benzquinoliue-3-carboxylic acid.

3. l-methyl-1,2,3,4-tetrahydro 5,6 benz-qumolme-3- carboxylic acid.

4. A 1-methyl-1,2,3,4-tetrahydro-5,6-benz qumohne- 3-carboxylic acid hydrohalide.

5. A salt of l-methyl-1,2,3,4-tetrahydro 5,6 benzquinoline-3-carboxylic acid methyl amlde.

6. 1-methyl-1,2,3,4-tetrahydro 5,6 benz-qu1nolme-3- carboxylic acid methyl amide.

7. A process which comprises treating a compound selected from the group consisting of l-dialkylammornethyl- Z-hydroxy-naphthalene, 1-piperidinomethyl-2-hydroxynaphthalene and 1-morpholinomethyl-Z-hydroxy-naphthalene with a methane derivative represented by the formula CH2(X)Y, where X is a radical selected from the group consisting of carbalkoxy, carbobenzyloxy and cyano radicals and Y is a radical selected from the group consisting of carbalkoxy and carbobenzyloxy radicals, in the presence of an alkali metal, subjecting the 3-subst1- tuted-3,4-dihydro-5,6-benz-coumarin formed to hydrogenolysis, treating the product so obtained with formaldehyde and an amine of the group consisting of piperidine, morpholine, methylamine and a compound of the formula NH(R)R", wherein R' is selected from the group consisting of methyl and ethyl and R" is selected from the group consisting of methyl, ethyl and benzyl, heating an alkali metal salt of the resulting 3-[2-hydroxynaphthyl( 1) -2-carboxy-propylamine derivative with methylamine under pressure.

8. A process which comprises treating a compound selected from the group consisting of l-dialkylaminomethyl-2-hydroxy-naphthalene, 1-piperidinomethyl-2-hydroxynaphthalene and 1-morpholinomethyl-2-hydroxy-naphthalene with a methane derivative represented by the formula CH2(X)Y, wherein X is a radical selected from the group consisting of carbalkoxy, carbobenzyloxy and cyano radicals and Y is a radical selected from the group consisting of carbalkoxy and carbobenzyloxy radicals, in the presence of an alkali metal, subjecting the 3-substituted-3,4-dihydro-5,6-benz-coumarin formed to hydrogenolysis, treating the product so obtained with formaldehyde and an amine of the group consisting of piperidine, morpholine, methylamine and a compound of the formula NH(R)R", wherein R is selected from the group consisting of methyl and ethyl and R" is selected from the group consisting of methyl, ethyl and benzyl, heating the resulting 3-[2-hydroxy-naphthyl-(1)l-2-carboxypropylamine derivative with methylamine under pressure and hydrolysing the amide produced.

9. A process which comprises heating an alkali metal salt of a compound represented by the formula COOH CHr-CH CHr-X OH wherein X is a radical selected from the group consisting of piperidino, morpholino, methylamine radicals and those of the formula -N(R')R", R being selected from the group consisting of methyl and ethyl, and R" being a radical selected from the group consisting of methyl, ethyl and benzyl, with methylamine under pressure to produce l-methyl-1,2,3,4-tetrahydro-5,6-benzquinoline-3-carboxylic acid.

10. A process which comprises heating a compound represented by the formula C0 OH CHPCH C Hr-X O H wherein X is a radical selected from the group consisting of piperidino, morpholino, methylamine radicals and those of the formula -N(R')R, R being selected from the group consisting of methyl and ethyl, and R" being a radical selected from the group consisting of methyl, ethyl and benzyl, with methylamine under pressure to produce l-methyl-1,2,3,4-tetrahydro-5,6-benz-quinoline- 3-carboxylic acid methylamide.

11. A process which comprises treating l-methyl- 1,2,3,4-tetrahydro-5,6-benz-quinoline-3-carboxylic acid methylamide with a hydrolyzing agent to produce l-methyl-l,2,3,4-tetrahydro-5,6-benz-quinoline-3-carboxylic acid.

No references cited. 

1. A COMPOUND OF THE GROUP CONSISTING OF 1-METHYL1,2,3,4-TETRAHYDRO-5,6-BENZ-QUINOLINE-3-CARBOXYLIC ACID, THE METHYLAMIDE THEREOF AND SALTS THEREOF. 